2-pyridyl-indenes



United States Patent Oilice Patented Jan. 2l, ll

3,ll3,395 Z-PYREDYL-NDENES Milton Joel Allen, S'amrnit, NJ., assigner to Ciba Corporation, a corporation of Delaware No Drawing. Filed Get. 25, 1960, Ser. No. 64,703 v6 Claims. (Cl. Zoll- 290) The presentinvention concerns indene compounds. It relates, more especially, to 3-lower alkyl-Q-pyridyl-indenes, particularly to compounds of the formula:

in which R represents hydrogen, halogeno, amino, nitro, as well as lower alkyl, substituted lower alkyl, particularly triluorornethyl, etherified hydroxyl, such as lower alkoxy, or etheriiied mercapto, such as lower alkyl-rnercapto, R1 stands for lower alkyl, R2 represents hydrogen or lower alkyl, and Py represents a pyridyl radical, salts, N-oxides or salts of N-oxides thereof, as well as process for the preparation of such compounds.

The group R, which may also stand for hydrogen, represents primarily halogeno, particularly chloro, as well as iluoro, bromo and the like. It may also stand for an amino group; the latter may be represented above all by N-unsubstituted amino, as well as substituted amino. The latter stands, for example, for N-lower alkyl-amino, eg. N-rnethylarnino, N-ethylamino and the like, or N,Ndi lower alkylarnino, eg. N,Ndimethylamino, N-ethyl-N- methyl-amino, ll,N-diethylamino and the like. An amino group may also be represented by N-acylamino, in which acyl represents the acyl group Aof an organic carboxylic acid containing from one to twenty carbon atoms, such as a lower aliphatic monocarboxylic acid, for example, a lower alkane monocarboxylic acid, eg. tormic, acetic, propionic, pivalic acid and the like, a lower alkene monocarboxylic acid, eg. 3-butene carboxylic acid and the like, a hydroxy-lower al'kane monocarboxylic acid, eig. glycolic, lactic acid and the like, a lower alkoxy-lower alkane monocarboxylic acid, eg. methoxy-acetic, ethoxy-acetic acid and the like, a lower alkanoyl-lower alkane monocarboxylic acid, eg. pyruvic acid and the like, a halogenolower alkane monocarboxylic acid, eg. triiluoroacetic, chloroacetic, dichloroacetic, trichloroacetic, bromoaceric acid and the like, a lower aliphatic dicarboxylic acid, for example, a lower alkane dicarboxylic acid, eg. oxalic, malonic, succinic, methylsuccinic, dimethylsuccinic, glutaric, x-inethylglutaric, ,u-dimethylglutaric, -methylglutaric acid and the like, a lower alkane dicarboxylic acid half ester wtih a lower alkanol, eg. s'uccinic acid monornetnyl ester, glutaric acid monoethyl ester and the like, a lower alkene dicarboxylic acid, eg, itaconic, homoitaconic, rnaleic, cit'raconic, homocitraconic, pyrocinchonic, xercnic, fumarie acid and the like, a lower alkene dicarboxylic acid half ester with a lower alkanol, maleic acid monoethyi ester and the like, a hydroxy-lower ,alkane dicarboxylic acid, eg. malic, tartaric acid and the like, as well as the optically active forms thereof, a lower alkoxy-lower alkane dicarboxylic acid, eg. na-dimethoxysuccinic and the like, a lower alkoxy-lower alkene dicarboxylic acid, eg. ethoxy-nialeic acid and the like, a halogene-lower alkane dicarboxylic acid, eig, chlorosuccinic, brornosuccinic acid and the like, a lower aliphatic tricarboxylic acid, for example, a lower alkane tricarboxylic acid, eg. tricarballylicy acid and the lik, a lower alkene tricarboxylic acid, eg. aconitic acid and the like,

a hydroxy-lo-wer alkane tricarboxylic acid, e.g. citric acid and the like, a cycloaliphatic monocarboxylic acid, such as a cycloalkane monocarboxylic acid in which cycloalkane contains from live to six carbon atoms as ring members, c g. cyclohexane carboxylic acid and the like, a cyclo-aliphatic dicarboxylic acid, such as a cycloalkene dicarboxylic acid in which cycloalkene contains from tive to six carbon atoms as ring members, eg.. tetrahydrophthalic acid and the like, a cycloaliphatic-lower aliphatic monocarboxylic acid, such as cyclo-alkyl-lower alkane monocarboxylic acid, in which cycloalkane contains from tive to six carbon atoms as ring members, eg. cyclopentylpropionic, cyclohexylacetic acid and the like, a monocyclic or bicyclic carbocyclic aryl carboxylic or carbocyclic aryl-lower aliphatic carboxylic acid, eg. benzoic, dihydrocinnamic, cinnamic, mandelic, salicylic, 4- aminosalicyclic, Z-phenoxy-benzoic, Z-acetosybenzoic acid and the like, or a monocyclic or bicyclic cmbocyclic aryl dicarboxylic acid, eg. phthalic acid and the like, a monocyclic or bicyclic heterocyclic aryl carboxylic acid, eg. nicotinic, isonicotinic, o-quinoline carboxylic, thienoic, furoic acid and the like, or any other suitable carboxylic acid. An acylamino group representing R may, therefore, be an N-lower alkanoylamino group, eg. N-acetylamino, N-propionylamino and the like, an N-rnonocyclic carbocyclic aroyl-arnino group, eig. N-benzoylamino, N- (3,4,S-trimethoxybenzoyi)-amino and the like, an N- rnonocyclic azacyclic aroyl-arnino group, eg. N-nicotinoylarnino, N-isonico-tinoylamino and the like, or any other amino group containing the acyl radical of one of the above-mentioned acids. R may also stand for nitro, as well as for lower alkyl, which contains preferably from one to four carbon atoms, eg. methyl, ethyl, n-propyl, isopropyl, tertiary butyl and the like, substituted lower alkyl, particularly triiiuoromethyl, as well as lower al-koxylower alkyl, e..g. l-methoxy-ethyl, Z-rnethoxy-ethyl, 2- ethoxy-ethyl methoxymethyl and the like, etheried hydroxyl, particularly lower alkoxy, in which lower alkoxy contains preferably from one to four carbon atoms, eg. methoxy, ethoxy, isopropyloxy, n-butyloxy and the like, or etheriied mercapto, particularly lower alkyl-mercapto, in which lower alkyl contains from one to four carbon ato-ms, eg. methylmercapto, ethylmercapto, iso-butylmercapto and the like.

The substituent R, which may be attached 'to any of the positions available Ifor substitution, is preferably located in the -position.

R1, representing lower alkyl, stands primarily for methyl; other lower alkyl radicals are, for example, ethyl, n-propyl, isopropyl and the like.

The radical R2 represents primarily hydrogen, but may also stand for lower alkyl, particularly methyl, ethyl and the like.

A pyridyl radical Py represents primarily 3-pyridyl or 4-pyridyl, as well as 2-pyridyl; these radicals may also be substituted in any of the available positions by one or more than one Iof the same or of different substituents; such substituents are, 'for example, lower alkyl, eg. methyl, ethyl and the like, lower alkoxy, eg. methoxy, ethoxy and the like, halcgeno, eg. iluoro, chloro, bromo and the like, or any other suitable substituent.

The Z-pyridyl-indene compounds of this invention may also forni therapeutically acceptable acid addition salts, particularly with inorganic acids, eg. hydrochloric, hydrobromic, nitric, sulfuric, phosphoric acids and the like, as well as with other acids, such as organic carboxylic acids, eg. formic, acetic, propionic, glycolic, lactic, 'pyruvic, oxalic, malonic, succinic, maleic, hydroxymaleic,` dihydroxymaleic, fumarie, malic, tartaric, citric,`be'nzoic, cinnarnic, madelic, salicyclic, 4-aminosalicyclic, 2-pl1enoxybenzoic, Z-acetoxybenzoic, nicotinic acids and the like, or

with organic sulfonic acids, c g. methane sulfonic, ethane sulfonic, Z-hydroxyethane sulfonic, benzene sulfonic, ptoluene sulfonic acids and the like.

Also included within the scope of the invention are N-oxides of the indenes of this invention and the salts of such N-oxides with acids, such as those with the previously mentioned acids.

The compounds of the present invention inhibit the function of the adrenal cortex, which is manifested in a decrease of hydrocortisone output in dog tests, as well as in a depression of the production of aldosterone and other corticosteroids in rat adrenal incubates. Adrenal cortex inhibitors, which cause a decrease of hydrocortisone and corticosterone, are known. But this decrease may be accompanied by a simultaneous increase of desoxycorticosterone and of ll-desoxy-17fx-hydroxy-corticosterone (Reichstein S), which steroids are possible precursors of hydrocortisone and corticosterone; this increase partially offsets the beneficial inhibition of the secretion of the latter. Contrary to the effects of these adrenal cortex inhibitors, the compounds of the present invention do not show such a shift in the secretion pattern; they have, therefore, greatly improved properties ovcr those of known adrenal cortex inhibitors. They can be used as agents in the treatment of conditions which are due to primary hyperfunction of the adrenal cortex, such as Cushings syndrome, primary aldosteronism and the like. They also have a beneficial effect in the treatment of secondary hyperfunction of that vital gland, such as secondary aldosteronism, which accompanies conditions such as liver cirrhosis, congestive heart failure, nephrotic syndrome and the like.

A pronounced inhibiting effect on the secretion of the adrenal cortex is exhibited by compounds of the formula:

in which R stands for halogeno particularly chloro, amino and nitro, and Py' stands for 3-pyridyl or 4-pyridyl. The 6chloro-3-methyl-2-(3-pyridyl)indene, the 3-methyl-6- nitro-Z-(S-pyridyl)-indene and the 6-arnino-3-methyl-2- (3-pyridyl)indene show outstanding adrenal cortex inhibiting effects.

The compounds of this invention may be used as medicaments in the form of pharmaceutical preparations, which contain the new 3-lower alkyl-Z-pyridyl-indene compounds or salts thereof in admixture with a pharmaceutical organic or inorganic, solid or liquid carrier suitable for enteral or parenteral administration. For making up the preparations there maybe employed substances, which do not react with the new compounds, such as water, gelatine, lactose, starches, stearic acid, magnesium stearate, stearyl alcohol, talc, vegetable oils, benzyl alcohols, gums, propylene glycol, polyalkylene glycols or any other inert carrier used in medicaments. The pharmaceutica preparations may be in the solid form, for example, as solutions, suspensions, emulsions and the like. If desired, they may contain auxiliary substances, such as preserving, stabilizing, wetting, emulsifying agents and the like, as wcll as salts for varying the osmotic pressure, buffers, etc. They may also contain, in combination, other useful substances.

Thc compounds of the present invention may be prepared, for example, by contacting a 2-phenyl-3-pyridylbutan2,3diol compound, particularly a compound of the formula:

l Rl

R Ill; (Hz--Rz @er-Cre OH OH in which R, R1, R2 and Py have the previously indicated meaning, or a salt thereof, with a strong Lewis acid and isolating the resulting indene compound, and, if desired, introducing into the aromatic carboxylic portion of a resulting indene compound a substituent, and/ or, if desired, converting in a resulting compound a substituent attached to the aromatic carboxylic portion of the indene nucleus into another substituent, and/ or, if desired, converting a resulting salt into the free compound, and/or, if desired, converting a resulting compound into a salt, an N-oxide or a salt of an N-oxide thereof.

Salts of the starting materials, such as those with mineral acids, e.g. hydrochloric, sulfuric, phosphoric acid and the like, may be formed in situ in the presence of the acidic medium used for the rearrangement of the diol.

Strong Lewis acids capable of bringing about the rearrangement and dehydrogenation of the diol compounds or the salts thereof, are especially strong inorganic acids, particularly hydrochloric acid, as well as hydrobromic acid, perchloric acid, sulfuric acid, phosphoric acid (for example, in the form of polyphosphoric acid), fluoboric acid and the like; hydrochloric acid is the preferred reagent. Advantageously, the reagents are used in concentrated form; concentrated aqueous hydrochloric acid is the reagent of choice. The simultaneous rearrangement and dehydration rnay be carried out at room temperature, but is preferably performed at an elevated temperature. Instead of carrying out the reaction at atmospheric pressure, a closed vessel may be utilized to provide increased pressure. To avoid contact with atmospheric oxygen, the reaction may be performed in the presence of an inert gas, eg. nitrogen.

A resulting mixture may be separated into the single compounds according to known methods such as, for example, crystallization and/ or recrystallization from different solvents or solvent mixtures, adsorption on an adsorbent, such as aluminum oxide, silicic acid, a diatomaceous earth and the like, and subsequent elution, formation of derivatives and sepaartion of derivatives from unreacted material (for example, any ketonic material may be eliminated from non-ketonic compounds by treating a mixture containing ketone compounds with a ketone reagent, such as, for example, a hydrazine compound, e.g. 2,4-dinitrophenylhydrazine, Girards reagent and the like and separating the ketone derivative from the unreactcd material), or and other suitable procedure.

The 2-phenyl-3-pyridyl-butan-2,3diol compounds, particularly the diols of the formula:

in which R, R1, R2 and Py have the previously given meaning, and their acid addition salts, which are used as the starting materials in the above reaction, are new and are intended to be included Within the scope of the invention. Particularly useful as starting materials are the diols of the formula:

CH3 CH3 OH OH in which R stands for hydrogen or halogeno, particularly chloro, and Py represents 3pyridyl or 4-pyridyl, and acid addition salts thereof; this group may be represented, for example, by 2-phenyl-3-(3-pyridyl)-butan 2,3 diol, 2 (4 chloro phenyl) 3 (3 pyridyl)- butan-2,3diol and acid addition salts thereof.

These diols may be prepared, for example, by subjecting a mixture consisting of a lower alkyl phenyl ketone, particularly a ketone of the formula:

in which R and R1 have the previously indicated meaning,

O=C-Py in which R2 and Py have the previously given meaning,

to a reduction procedure, and isolating the desired diol, especially the compound of the formula:

in which R, R1, R2 and Py have the previously given meaning, and, if desired, introducing into the phenyl portion a substituent, and/or, if desired, converting a substituent in the phenyl portion into another substituent, and/or, if desired, converting a resulting salt into the free base, and/or, if desired, converting a free compound into a salt thereof.

The reduction procedure may be carried out according to methods used for the preparation of analogous diols. For example, a solution of the mixture in a proper solvent or solvent mixture, for example, a mixture of a lower alkanol, e.g. methanol, ethanol and the like, and water, or any other appropriate solvent system, may form the catholyte in an electrolytic reduction procedure. Additional substances, which enhance the reduction, such as salts, for example, alkali metal salts of organic acids, e.g. sodium acetate, potassium acetate and the like, may be present in the catholyte. A suitable solution, such as, for example, an aqueous solution of potassium carbonate and the like, may serve as an anolyte. The two electrolytes may be separated by a diaphragm, such as an ion exchange resin membrane, porous porcelain membrane, parchment and the like. The reduction is generally performed on a cathode having a high overpotential and at an initial current density greater than about 0.1 amp/cm?. Cathodes of high overpotential are, for example, those which have an overpotential equal to or higher than cadmium, such as mercury, lead amalgam, lead and the like. Any appropriate anode, such as nickel, platinum, carbon, lead, stainless steel and the like, may be employed. An initial current density higher than about O l amp/cm.2 is sufficient to form the desired diol compound; however, for practical reasons an initial current density higher than about 0.5 amp/cm.2 may diminish the efficiency of the process due to increased hydrogen evolution.

The reduction procedure may also be carried out, for example, by irradiating the previously mentioned mixture of the two ketones with light, particularly ultraviolet light, in the presence of a hydrogen donor, such as a secondary lower alkanol, especially isopropanol, or any other suitable reagent. The irradiation may be carried out at room temperature or at an elevated temperature.

The reduction of a mixture of the two ketones having the previously mentioned formulae may give rise to a mixture of different products; these products are mainly the desired asymmetrically substituted diol and the symmetrically substituted diols formed by dimerization ofthe two secondary alcohols resulting from the ketones. The desired asymmetrically substituted diol may be separated from the symmetrically substituted diols according to known methods, for example, by fractionated extraction, fractionated distillation and/or adsorption on a suitable adsorbent, e.g. aluminum oxide and the like, and subsequent elution and the like.

Substituents may be introduced into the aromatic carbocyclic portions of the indene compounds or the diols used as the starting materials for the preparation of the inuenes. Thus, upon nitration, for example, with concentrateo nitric acid at a low temperature, a nitro group may be introduced into tne aromatic carbocycl'ic portion of an indene compound resulting from the previously described procedure or into the phenyl portion of a -2-phenyl-3-pyridyl-butan-2,3diol compound.

Furthermore, in a resulting indene compound or in a diol used as the intermediate, a substituent attached to the aromatic carbocyclic portion may be converted into another substituent. For example, a nitro group may be converted into an amino group according to known methods, for example, by treatment with nascent hydrogen, which may be generated by the action of an acid on appropriate metals, e.g. hydrochloric acid on tin, iron and the like, or any other suitable reduction procedure. The reduction may be carried out in the presence of an alkylating reagent such as, for example, a lower alkanal, e.g., formaldehyde and the like; the nitro group or" the starting material may thus be converted directly into an N-substituted amino group, such as, for example, the N,N dimethyl-amino group and the like, or, an N-unsubstituted amino group may be converted into an N-substituted amino group. For example, a primary amino group may be alkylated according to known procedures, such as a reductive alkylation reaction, particularly the Leuckart reaction, which utilizes primarily formaldehyde in the presence of formic acid as the alkylating reagent. A free amino group may also be converted into the N-acylamino group; acylation is carried out according to known procedures, such as treatment with a reactive derivative of carboxylic acid, particularly a halide, e.g. chloride and the like, or an anhydride, if necessary in the presence of an organic base, e.g. pyridine. in addition, a free amino group may be converted into a halogeno atom; for example, the compound containing an amino group may be diazotized by treatment with nitrous acid (from an alkalipmetal, e.g. sodium, nitrite in the presence of an excess of a mineral, e.g. hydrochloric acid) and the resulting diazonium salt is reacted with a cuprous halide, e.g. cuprous chloride and the like, according to the Sandmeyer procedure.

The compounds of this invention may form therapeutically acceptable acid addition salts, particularly with mineral acids, e.g. hydrochloric, nitric, sulfuric acid and the like, or any other suitable acids. Salts may be obtained according toknown methods, for example, by reacting the free base with the appropriate inorganic or organic acid; for example, a solution of the free base in a lower alkanol, e.g. methanol, ethanol, n-propanol, isopropanol and the like, an ether, e.g. diethylether, tetrahydrofuran, p-dioxane and the like, a lower alkanone, e.g. acetone and the like, a halogenated hydrocarbon, e.g. methylene chloride, chloroform, ethylene chloride and the like, or any other suitable solvent, may be treated with the acid or a solution thereof and the resulting salt may be isolated or may be used in solution without isolation. Salts of the new compounds of this invention may be converted into the free bases, for example, by treatment with an alkaline reagent, such as an alkali metal hydroxide, e.g. sodium hydroxide, potassium hydroxide and the like, ammonia, an anion exchange resin and the like.

The compounds of the present invention may also form N-oxide derivatives, which may be obtained, for exampie, by treating the tertiary base with an N-oxidizing reagent, particularly with a peracid, such as an inorganic peracid, e.g. persulfuric acid and the like, an organic percarboxylic acid, e.g. peracetic, perbenzoic, perphthalic acid and the like, or an organic persulfonic acid, e.g. ptoluene persulfonic acid and the like, or with ozone, preferably in a suitable inert solvent. N-oxides may form salts with acids, which may be prepared, for example, according to the procedure mentioned hereinbefore for the salt formation.

The invention also comprises any modification of the general process wherein a compound obtainable as an intermediate at any stage of the process is used as starting material and the remaining step(s) of the process is (are) Ycarried out, a's well as any new intermediates.

In the process of this invention such starting materials 7 are preferably used which lead to inal products mentioned in the beginning as preferred embodiments of the invention.

The following examples are intended to illustrate the invention and are not to be construed as being limitations thereon. Temperatures are given in degrees centigrade.

Example 1 A solution of 2.26 g. of 2-(4-chloro-pher1yl)-3-(3- pyridyl)-butan-2,3diol in 30 ml. of concentrated aqueous hydrochloric acid is reliuxed for six hours. A precipitate is formed upon neutralizing the reaction mixture with concentrated aqueous sodium hydroxide and is filtered oit. The resulting 6-chloro-3-methyl-2-(3-pyridyl) -indene of the formula:

is recrystallized from a mixture of ethanol and Water and melts at 99.

The starting material may be prepared as follows: To a solution of 2.42 g. of 3-acetyl-pyridine and 3.09 g. of 4chloroacetophenone in 25 ml. of ethanol is added 15 fg. of potassium acetate in 17 ml. of water and placed into the cathode chamber containing a mercury cathode with a surface f 17.2 cm?. An Alundum membrane separates the catholyte from the anolyte, which consists of a 40 percent aqueous solution of potassium carbonate. A nickel electrode is used as the anode. The electrolysis is carried out at a catholyte temperature of 83 (reuxing) and at a reference potential of 1.7 volts vs. a standard calornel electrode; the initial current is 6.8 amps., which drops to a iinal current of 0.2 amp. after 30 minutes.

The catholyte s removed and concentrated to a small volume under reduced pressure; upon chilling an oily precipitate is formed, which is collected and washed with water. A solution of the solid material in n-butanol is extracted with 1 N aqueous hydrochloric acid. The acidic extracts are made basic with concentrated aqueous sodium hydroxide and extracted with n-butanol. The organic layer is evaporated to dryness, the residue is dissolved in benzene, the benzene solution is iiltered and the filtrate is placed on a column containing aluminum oxide (neutral, activity No. 3). The column is Washed with benzene and then eluted with a 3:1-mixture of benzene and diethylether. The solvents are evaporated from the eluate, the residue is distilled and the desired diol is collected at 160/0.001 mm. The distillate is triturated with n-pentane to yield the 2-(4-chloro-phenyl) 3-(3-pyridyl)-butan-2,3diol of the formula:

which melts at 86-90".

Upon treatment of 2-(4-chloro-pheny1)-3-(4-pyridyl) butan2,3diol, 2-(4-bromopheny1)3(3-pyridyl)butan 2, 3-diol, 2- (4-iiuoro-phenyl) -3- 3-pyridyl) butan-2,3diol or 3 (4 chloro phenyl) 4 (3 pyridyl) hexan- 3,4diol (which diols may be prepared according to the method shown hereinbefore by selecting the appropriate starting materials) with a strong Lewis acid, e.g. concentrated aqueous hydrochloric acid and the like, according to the above-given procedure, the 6-chloro-3-methyl-2- (4-pyridyl)indene, 6bromo-3-methyl2(3-pyridyl)in dene, 6-uoro-3-methyl-2-(Ii-pyridyl)-indene and the 6- chloro 3 ethyll methyl 2 (3 pyridyl) indene, respectively, are being formed.

Example 2 A solution of 12.5 g. of 2phenyl-3-(3pyridyl)butan 2,3-diol in 700 ml. of concentrated aqueous hydrochloric acid is relluxed for 48 hours. Charcoal is added, reflux ing is continued for an additional half hour and the reaction mixture is then iiltered through a diatomaceous earth preparation, the yfiltrate is made basic, the organic material is extracted with diethylether and the ether layer is separated and dried. After evaporation of the solvent, the oily 3-methyl2(3pyridyl)-indene of the formula:

is recrystallized from 40 percent aqueous ethanol, M.P. SSLS-60.5; yield: 4.55 g.

The starting material may be prepared as follows: A solution of 57.4 g. of 3-acetyl-pyridine and 57.2 g. of acetophenone in 590 ml. of ethanol and a solution of 354 g. of potassium acetate in 400 ml. of water are placed in the cathode chamber; anolyte, cathode, anode, membrane and temperature are identical with those described in Example 1. The electrolytic reduction is carried out at a reference potential of -2 volts vs. a standard calomel electrode; the initial current is 17.5 amps., the final current 2.4 amps. and the reaction time 230 minutes. The catholyte is worked up as shown in Example 1 to yield 10.34 g. of 2-phenyl-3*(3pyridyl) butan-2,3diol of the formula:

which is about percent pure and is used without further purification.

Example 3 is recrystallized from hexane, M.P. 126-l28; yield: 0.73 g. (54 percent).

Upon treatment of 6-amino-3-methyl-2-(3-pyridyl) indene with nicotinoyl chloride in pyridine the desired 3 -methyl-G- (N-nic otinoyl-amino -2- 3 -pyridyl -indene is being formed.

The starting material may be prepared as follows: To i 2.95 g. of 3methyl2(3pyridyl)-indene is added portionwise ml. of concentrated nitric acid while stirring and cooling to 0. The temperature is maintained for an additional two hours with occasional agitation and the reaction mixture is then poured into 2000 ml. of a mixture of ice water. After standing for thirty minutes, the yellow precipitate is filtered olf to yield 2.51 g.

of 3-rnethyl-6-nitro-2-(3-pyridyl)-indene nitrate of the formula:

which is recrystallized from 95 percent ethanol, M.P. 165 (with decomposition).

Compounds, which may also be prepared according to the above-described procedures are, for example, 6-amino- 3-methyl-2-(4-pyridyl)-indene, 3-methyl-6-Nmethylamino 2(3pyridyl)indene, 6-N,Ndimethylamino3-methyl-2-(3- pyridy1)indene, 3,6-dimethyl-2(3-pyridyl)indene, 3- methyl-2-(4-pyridyl)-G-triuoromethyl-indene, 6-methoxy 3-methyl2-(3-pyridyD-indene, 6-isopropyloxy-3-methyl-Z- (4pyridyl)indene, 3-methyl-6-methy1mercapto-2-(6-methyl3-pyridy1)indene, 6-chloro-3-ethy1-l-methyl-Z-(B-pyridyl)indene and the like; the appropriate starting materials may be obtained according to the previously described procedures.

Example 4 A solution of 0.05 g. of 6amino-3-methyl-2(3-pyridy1)indene in 2 ml. of concentrated hydrochloric acid is chilled to in an ice-bath, to which is added while stirring, a cold solution of 0.02 g. of sodium nitrite in 1 ml. of water over a period of ten minutes. After an additional fifteen minutes of stirring, the solution is poured into a cold, stirred solution of 0.03 g. of cuprous chloride in 1.5 ml. of hydrochloric acid of 28 percent strength. After thirty minutes, the mixture is allowed to warm to room temperature and stirring is continued for three hours. It is then heated to 70 on a water bath, the red solution is decanted, chilled, made basic and extracted with diethyl ether. The organic solution is dried and evaporated; the residue is taken up in i0 pentane and the solution is slowly evaporated to yield the 6-chloro-3methyl-2(3pyridyl)indene, which is identical with the compound described in Example 1.

What is claimed is: 1. A member selected from the group consisting of a compound of the formula References Cited in the tile of this patent UNITED STATES PATENTS 2,798,888 Ueberwasser a July 9, 1957 2,909,525 Fand Oct. 20, 1959 2,947,756 Huebner Aug. 2, 1960 2,971,000 Mathes et al. Feb. 7, 1961 2,982,783 Schenck May 2, 1961 OTHER REFERENCES Culvenor: Rev. of Pure and Applied Chem., vol. 3, No. 2, pp. 83-86 (1953). 

1. A MEMBER SELECTED FROM THE GROUP CONSISTING OF A COMPOUND OF THE FORMULA 